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A novel peroxisome proliferator-activated receptor (PPAR) α/δ dual agonist 5c was developed with an EC 50 of 8 nM for PPARα, 5 nM for PPARδ, and &gt;300-fold selectivity against PPARγ (EC 50 = 2939 nM), respectively. Further ADME and pharmacokinetic studies indicated 5c possessed distinguished in vitro and in vivo profiles. The excellent in vivo efficacy of compound 5c was demonstrated by the rat primary biliary cirrhosis (PBC) model.

Discovery of a Novel Selective Dual Peroxisome Proliferator-Activated Receptor α/δ Agonist for the Treatment of Primary Biliary Cirrhosis